# Identification and clinical validation of endoplasmic reticulum genes related to pulmonary tuberculosis

## TL;DR

This study identifies ER stress-related genes linked to tuberculosis and validates IL-1B as a key player in the disease's progression and immune response.

## Contribution

The study introduces a set of ER stress-related genes and validates IL-1B as a diagnostic marker for tuberculosis.

## Key findings

- Ten ER stress-related differentially expressed genes were identified in tuberculosis.
- IL-1B showed high diagnostic performance and was confirmed to be elevated in TB patients.
- IL-1B is strongly associated with M1 macrophage infiltration and inflammatory markers like IL-6 and TNF-α.

## Abstract

Tuberculosis (TB), caused by Mycobacterium tuberculosis (MTB), is a serious infectious disease. Previous studies have shown that endoplasmic reticulum (ER) stress plays an important role in various infectious processes. This study aimed to identify potential ER stress-related genes in TB by analyzing differentially expressed genes (DEGs) and to explore the role of ER stress in MTB infection. Ten ER stress-related DEGs (ERSRDEGs) were identified by standardizing and analyzing differential expression in the dataset GSE114911. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses revealed that these ERSRDEGs are significantly involved in neutrophil migration and the IL-17 signaling pathway. A protein-protein interaction network identified four hub genes (IL-1B, CCL20, IL -1 A, and TNF), among which gene IL-1B showed highly significant differential expression in the independent dataset GSE147964, demonstrating excellent diagnostic performance (AUC = 0.93). This finding was further validated by Enzyme-linked immunosorbent assay (ELISA), which confirmed high expression of IL-1B in the plasma of TB patients. Immune infiltration analysis showed increased infiltration of M1 macrophages in the TB infection group, with gene IL-1B strongly positively correlated with M1 macrophage abundance. Additionally, the study analyzed correlations between genes IL-1 A and IL-1B and clinical indicators, including inflammatory factors and D-dimer levels. The results indicated that gene IL-1B was positively correlated with IL-6, TNF-α, and IFN-γ, while gene IL-1 A was positively correlated with D-dimer. Overall, these findings emphasize the critical role of ER stress-related genes in the pathophysiology of MTB infection.

The online version contains supplementary material available at 10.1038/s41598-025-29599-7.